庆大霉素发酵工艺规程FATS-PP-F(J-701)-GMC

庆大霉素发酵工艺规程FATS-PP-F(J-701)-GMC 庆大素庆酵工庆庆程霉 Fermentation Process Procedure of Gentamicin Sulfate 庆行日期,20089 年 912 月 21 日 2011 年 11 月 10 日 stExecutive date: 12110 September December November 20 0 9 11 庆行日期,2008 年 10 月 15 日 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: thExecutive date: 15 October 2008 庆行日期,2007 年 12 月 1 日 thExecutive date: 1 December 2007Fujian Fukang Pharmaceutical Co., Ltd. Page: 2 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 本硫酸庆大素庆酵工庆庆程已由下列人庆庆庆批准霉并 Fermentation Process Procedure of Gentamicin Sulfate has been reviewed and approved by the following personnel 文件庆任庆 位庆 字日 期 Document responsibilityTitleSignatureDate 起草者庆庆技庆主任 Technical managerWritten by 庆核者 QA Reviewed by 庆核者QA庆理 Reviewed byQA Manager 批准者庆工程庆 QA&QC DirectorApproved by Fujian Fukang Pharmaceutical Co., Ltd. Page: 3 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 目 庆 Content 1 庆品述概API description31.1 庆品名称API name31.2 化庆庆式学构Chemical structure31.3 理化性庆Physicochemical property31.4 庆品有效期Shelf life32原庆材料和工庆用水庆量庆准 4 Specification for raw materials and process water 2.1 原庆材料的庆量庆准Specification for raw materials42.2 工庆用水的庆量庆准Specification for process water893工庆及庆庆 流程 快递问题件怎么处理流程河南自建厂房流程下载关于规范招聘需求审批流程制作流程表下载邮件下载流程设计 庆11 Flowchart of manufacturing process and equipment flowchart12 113.1 工庆流程庆Flowchart of manufacturing process 12 113.2 庆庆流程庆Equipment flowchart;庆附件, 12 124 工庆庆程Manufacturing process 2 124.1 庆子工庆庆程Manufacturing process of spores 4 154.2 庆酵工庆庆程Manufacturing process of fermentation 65 中庆庆品的庆量庆准和庆庆方法中庆控制的庆量庆准和庆庆方法19 Specification and analytical method of in-process materials21 195.1 中庆控制庆品的庆量庆准Specification of in-process materials 21 195.2 中庆控制庆品的庆庆方法Analytical method of in-process materials 21 246 三庆庆理Waste treatment 67 操作工庆生庆周期与 Process duration and manufacturing period 247 8 主要庆庆一庆 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf - Equipment list 6Fujian Fukang Pharmaceutical Co., Ltd. Page: 4 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 259 8 庆算公式Calculation formula65 7附件 Attachments10 附庆 Attachments Fujian Fukang Pharmaceutical Co., Ltd. Page: 5 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 1 庆品述概 API description1、庆品述 概API description 1.1庆品名 称API name 硫酸庆大素 ;霉GentamicinGENTAMYCIN SULFATE,又名硫酸艮素。它霉 庆大素庆庆庆色小庆庆菌;霉Micromonospora Purpurea,庆酵代庆庆生的一族基糖庆庆抗生氨 素,由 C,C和C等庆庆成份,各庆二分子半或二分子硫酸庆合成庆庆硫酸庆大素份与即霉,其成121a 品折干效价庆庆590µg/mg以上。 Gentamicin produced by Micromonospora purpurea is an aminoglycoside antibiotic with several components, such as Gentamicin C, Gentamicin C and Gentamicin C. Each 121a component is salified with 2 or 2.5 sulfuric acid molecule, that is gentamicin sulfate with potency of more than 590µg/mg on anhydrous basis. 目前庆大素的生庆是采用四庆庆酵霉,庆提庆后制成硫酸庆大素。霉 Gentamicin is manufactured using derived from four-level fermentation and subjected to extraction to form Gentamicin sulfate. 1.2化庆庆式 学构Chemical structure GentamicinRRR123 CMeNHMeH1 CMeNHH22 CHNHH1a2 CHNHMe2a2 1.3理化性庆Physiochemical property 本品庆白色或接近白色粉末;无臭;有引性湿,易溶于水,在乙醇、丙庆、庆或乙庆中不溶仿。 The substance is a white or almost white, odourless and hygroscopic powder, freely soluble in water, practically insoluble in alcohol, acetone, chloroform or ether. Fujian Fukang Pharmaceutical Co., Ltd. Page: 6 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 1.4庆品有效期Shelf life 根据庆定性究庆果～研硫酸庆大素庆品有效期霉定庆四年;庆附件,。 The shelf life of gentamicin sulfate is four years, see attachment.1.5 庆存件 条Storage condition 密封～在干燥庆保存。 Preserve in tightly closed containers, stored in a dry place.Fujian Fukang Pharmaceutical Co., Ltd. Page: 7 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 2、原庆材料和工庆用水庆量庆准 Specification for raw materials and process water2.1 原庆材料的庆量庆准 Specification for raw materials 序号原庆材料的名称企 庆 庆 准庆 注 No.Raw materialsIn-house criteriaRemark 外 庆,白色粉末,无味庆庆霉 Appearance: White powder, no mildew or rot. 庆 庆,取本品庆0.1g加水20ml混匀,加庆液滴碘数, 即庆庆色或庆黑色,加庆后逐庆褪色,放冷,庆色庆庆。 玉米淀粉Identification: To 0.1g, add 20ml water with 1Corn starchstirring, then add a few drops of iodine solution, a RM-102blue or bluish black color produced. Under heating, it is decolorizing gradually. After cooled, the blue color reappears. 水 分Water,庆15.0%. 含 量Assay,庆78.0%. 外 庆,色或淡色粉末黄黄,无味庆庆。霉 Appearance: yellow or yellowish powder, no 玉米粉mildew or rot. 2Corn meal水 分Water,?14.0%. RM-103庆 度Fineness,?72% (80目庆pass 80 meshes screen). 含 量Assay,?70.0%. Fujian Fukang Pharmaceutical Co., Ltd. Page: 8 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 序号原庆材料的名称企 庆 庆 准庆 注 No.Raw materialsIn-house criteriaRemark 庆大素庆酵霉 要求冷榨 外 庆,淡色粉末黄,无味庆庆。霉 Processed Appearance: Yellowish powder, no mildew or rot. by cold 黄豆庆粉蛋白庆Protein,?37.0%. pressing 3Soybean meal水 分Water,?12.0%. only for RM-105庆 度Fineness,?72% (80目庆pass 80 meshes useused in screen). gentamicin 含油量Oil Assay (粗脂肪crude fat),?9.0%. fermentation (80)? 性 ,无色庆晶或白色庆晶性或庆粒性粉末、无臭状、 味。甜 Appearance: Colorless crystal or white crystalline or granular powder; odorless; taste sweet. 庆 庆,取本品庆0.2g,加水5ml溶解后,庆庆滴入庆的温 碱性酒石酸庆庆液中,即氧沉生成化庆庆的庆色淀。 Identification: Dissolve 0.2 g of sample with 5 ml of water and slowly drop in warm alkaline copper 葡萄糖tartrate solution to produce red precipitate of 4Glucosecuprous oxide. RM-111比旋度Specific rotation:+52.5? ~ +53.0?. 酸 度,取本品庆2g,加水20ml溶解后,加庆指示酚 液3滴庆庆化庆液;与氧0.02mol/L,0.2ml庆庆粉庆色。 Acidity: Dissolve 2 g of sample with 20 ml of water and add 3 drops of phenolphthalein indicator and 0.2 ml of 0.02 mol/L NaOH solution to produce pink color. 干燥失重Loss on drying,?9.5%. 庆灼渣残Residue on ignition,?0.1%. Fujian Fukang Pharmaceutical Co., Ltd. Page: 9 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 序号原庆材料的名称企 庆 庆 准庆 注No.Raw materialsIn-house criteriaRemark 外 庆,色至土色粉末浅黄黄,无庆庆。 Appearance: yellowishYellow to yellowish brown 蛋白庆powder, no lumps formed.5Peptone庆 磷Total P,?0.20%. RM-201庆 氮Total N,?13.0%. 水 份Water,?7.0%. 硫酸灰份Sulfate ash,?7.0%. 外 庆,棕色粉末黄,无潮解庆庆。 Appearance: Yellowish brown powder, no 淀粉庆 deliquescence and no lump.6Amylase 庆 度Fineness,?80%(40目庆准庆通庆pass 40 RM-205 meshes)。 活 力Activity,?2000r/g。 外 庆,白色庆晶。 Appearance: White crystals. 硝酸庆 庆 庆,本品呈庆庆和硝酸庆的庆庆反庆 7Potassium nitrate Identification: Positive reaction for potassium and RM-209 nitrate. 含 量Assay:?99.0%. 外 庆,庆白色庆晶, 无可庆机械庆庆。 Appearance: Almost white crystals, no visible mechanical impurities. 硫酸庆 庆 庆,本品庆硫酸庆和庆庆的庆定反庆。 Ammonium 8Identification: Positive for ammonium and sulfate sulfate ID reaction. RM-215 含 量Assay ((NH)SO)～?96.0%。424 游酸含量离Free acid (calculated as HSO): 24 ?0.05%. Fujian Fukang Pharmaceutical Co., Ltd. Page: 10 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 序号原庆材料的名称企 庆 庆 准庆 注No.Raw materialsIn-house criteriaRemark 外 庆～白色粉末。 Appearance: White powder. 庆 庆,本品庆酸庆和庆庆的庆定反庆。碳 Identification: Positive for calcium and carbonate 碳酸庆;庆庆, ID reaction. Calcium 碳酸庆;以CaCO干庆,,?97.0%.39carbonate Calcium carbonate (on dry basis) (lightweight) 水 分Water,?0.80%. RM-231 游离碱 (以CaO庆) ,?0.15%. Alkalinity (calculated as CaO) 庆 度Fineness,庆 98% (120目庆pass 120 meshes screen)。 外 庆,本品庆庆色或庆紫色庆晶,溶于水及乙庆。 Appearance: Red or purplish red crystals, soluble in 庆化庆water and ether. 10Cobalt chloride庆 庆,本品呈庆化物和庆庆的庆定反庆。 +RM-237Identification: Positive reaction for cobalt saltsCo +- and chloridesCl. 含 量Assay (CoCl?6HO): ?98.0%.22 外 庆,无色至淡色透明油液。黄状体 泡庆(GPE型) Appearance: Colorless to yellowish, transparent Defoamer 11oily liquid. (GPE type)o庆 点Turbidity point,13.0-21.5C。 RM-301 酸 庆Acidity,<0.5mg KOH/g。 Fujian Fukang Pharmaceutical Co., Ltd. Page: 11 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 序号原庆材料的名称企 庆 庆 准庆 注 No.Raw materialsIn-house criteriaRemark 外 庆,无色至淡紫色粘稠液。状体 液庆庆化庆体氧Appearance: Colorless to light purple viscous Liquid Sodium liquid. Hydroxide庆 庆Identification, RM-307;1,庆庆庆遇本品的水溶液庆庆色。酚 12 The color of the solution changes to red when react with phenolphthalein. ;2,本品庆庆庆的火焰反庆。 Positive reaction for sodium. 庆化庆含量氧Sodium hydroxide Assay,?30.0%。 外 庆,无色透明液。体 氨水Appearance: Colorless and transparent liquid. Ammonium 庆 庆,本品遇奈氏庆液呈棕色庆庆。 13 HydroxideIdentification: Produce brown turbidity when meets RM-311Nesser test solution. 含量氨Ammonia Assay,?18.0%。 Fujian Fukang Pharmaceutical Co., Ltd. Page: 12 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 2.2 工庆用水的庆量庆准Specification for process water (Portable water) 生活庆用水庆生庆准 控制庆目企 庆 庆 准Acceptance criteria of Testing itemsIn-house criteriapotable water in China GB 5749—2006 1.微生物指庆 Microbial items 庆大庆菌群 Total Coliforms /不得庆出不得庆出(MPN/100mL 或 CFU/100mL)Maximum 0 CFU/mlMaximum 0 CFU/ml 耐庆大庆菌群 不得庆出不得庆出Themotolerant coliform bacteria Maximum 0 CFU/mlMaximum 0 CFU/ml/(MPN/100mL 或 CFU/100mL) 大庆埃希氏菌 Escherichia coli不得庆出不得庆出/(MPN/100mL 或 CFU/100mL)Maximum 0 CFU/mlMaximum 0 CFU/ml 菌落庆数 Microbial Count / 庆100庆100 ;CFU/100mL, 2.毒理指庆 Toxicological items 砷 As /(mg/L)庆0.01庆0.01 庆0.01庆 Cadmium /(mg/L)庆0.005庆0.005 6+庆;六价,Cr/(mg/L)庆0.05庆0.05 庆 Pb/(mg/L)庆0.01庆0.01 汞 Hg/(mg/L)庆0.001庆0.001 硒 Se/(mg/L)庆0.01庆0.01 庆化物 Cyanide/(mg/L)庆0.05庆0.05 氟化物 Fluoride/(mg/L)庆1.0庆1.0 硝酸庆;以 N 庆,/(mg/L) 庆10(地下水源限制庆庆庆20, 庆10(地下水源限制庆庆, in Nitratein case of limited ground case of limited ground (calculated on nitrogen)water source)water source ?20) 三庆甲庆 Chloroform /(mg/L)庆0.06庆0.06四庆化碳 Carbon tetrachloride /(mg/L)庆0.002庆0.002 庆酸庆;使用臭庆,氧/(mg/L) 庆0.01庆0.01Bromate (For process using ozone) Fujian Fukang Pharmaceutical Co., Ltd. Page: 13 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 甲庆;使用臭庆,氧/(mg/L) 庆0.9庆0.9Formaldehyde (for process using ozone)庆庆酸庆;使用二化庆消毒庆,氧 Chlorite (for sterilization process using 庆0.7庆0.7 chlorine dioxide ) /(mg/L) 庆酸庆;使用庆合二化庆消毒氧 庆,Chlorate (for sterilization process 庆0.7庆0.7using chlorine dioxide ) /(mg/L) 3.感官性和一般化指庆状学 Sensory, characters and chemical items 不超庆 15 度不超庆 15 度 色度;庆庆色度庆位,Not more intensely colored Not more intensely colored Color (Platinum-Cobalt Scale)than degree 15 of reference than degree 15 of reference solutionsolution 不超庆 1 度不超庆 1 度 ;水源庆水技庆件限制与条;水源庆水技庆件限制与条 庆不超庆 3 度,庆不超庆 3 度, 庆庆度;散色庆庆度庆位,Not more intensely colored Not more intensely colored Turbidity degree (color and turbidity than degree 1 of reference than degree 1 of reference unit) /NTUsolution (not more solution (not more intensely colored than intensely colored than degree 3 of reference degree 3 of reference solution, when the water solution, when the water 臭和味无臭、味异异无臭、味异异 Odor and TasteOdorless and tastelessOdorless and tasteless 肉眼可庆物无无 Visible SubstancesNoneNone pH6.5,8.56.5,8.5 庆 Aluminum/(mg/L)庆0.2庆0.2 庆 Ion/(mg/L)庆0.3庆0.3 庆 Manganese/(mg/L)庆0.1庆0.1 庆 Copper /(mg/L)庆1.0庆1.0Fujian Fukang Pharmaceutical Co., Ltd. Page: 14 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 庆 Zinc /(mg/L)庆1.0庆1.0 庆化物 Chloride /(mg/L)庆250庆250 硫酸庆 Sulphate /(mg/L)庆250庆250 溶解性庆固体 庆1000庆1000 Total soluble solid/(mg/L) 庆硬度;以 CaCO3 庆, Total hardness庆450庆450(Calculated on CaCO3)/(mg/L) 庆3庆3耗量;氧COD Mn 法～以 O庆,2 ;水源限制～原水耗量氧;水源限制～原水耗量氧COD (COD Mn method, calculated as >6 mg/L 庆 庆5,>6 mg/L 庆 庆5, O)/(mg/L)2(?5, in case of limited (?5, in case of limited water source with COD>6 water source with COD>6 庆庆庆;以庆,酚苯酚 Volatile phenols庆0.002庆0.002(Calculated on phenol)/(mg/L) 庆子合成洗庆庆离 庆0.3庆0.3Synthetic Anionic detergent/(mg/L) 4.放射性指庆 Radioactivity items 庆 α 放射性 庆0.5庆0.5Total α radioactivity /;Bq/L, 庆 β 放射性 庆1庆1Total β radioactivity /;Bq/L, 5.消毒庆指庆 Disinfector itemsFujian Fukang Pharmaceutical Co., Ltd. Page: 15 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 与触水接 30min 后出水厂 中限庆 30 minutes 游余庆离(庆及游庆制庆气离)after?4mg/L;出水中余厂 Free Chlorine Residue 量 in finished 0.05~1.1mg/L(Chlorine and free chlorine preparation)water?0.3mg/L;管末梢网 水中余量 in tap water?0.05mg/L. 庆注,企庆庆庆庆告庆只庆臭和味、肉眼可庆物、菌落庆、庆大庆菌群、游余庆;庆及游庆制体数离气离 庆,。其余庆目庆水庆庆庆站庆告。 Note: The testing items conducted in-house are Odor and Taste, Visible Substances, Microbial Count, Total Coliforms and Free Chlorine Residue (Chlorine and free chlorine preparation). The other testing results are shown in the report from local Water Monitoring Institute. 生活庆用水庆生庆准 控制庆目Acceptance criteria of 企 庆 庆 准 Testing itemspotable water in ChinaIn-house criteria GB 5749—2006 1.微生物指庆 Microbial items 庆大庆菌群 Total Coliforms /不得庆出不得庆出(MPN/100mL 或 CFU/100mL)Maximum 0 CFU/mlMaximum 0 CFU/ml 耐庆大庆菌群不得庆出不得庆出Themotolerant coliform bacteriaMaximum 0 CFU/mlMaximum 0 CFU/ml/(MPN/100mL 或 CFU/100mL) 大庆埃希氏菌 Escherichia coli不得庆出不得庆出/(MPN/100mL 或 CFU/100mL)Maximum 0 CFU/mlMaximum 0 CFU/ml菌落庆数 Microbial Count /庆100庆100;CFU/100mL, 2.毒理指庆 Toxicological items 砷 As /(mg/L)庆0.01庆0.01庆0.01 庆 Cadmium /(mg/L)庆0.005庆0.005 6+庆;六价,Cr /(mg/L)庆0.05庆0.05Fujian Fukang Pharmaceutical Co., Ltd. Page: 16 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 庆 Pb/(mg/L)庆0.01庆0.01 汞 Hg/(mg/L)庆0.001庆0.001 硒 Se/(mg/L)庆0.01庆0.01 庆化物 Cyanide/(mg/L)庆0.05庆0.05 氟化物 Fluoride/(mg/L)庆1.0庆1.0硝酸庆;以 N 庆,/(mg/L) 庆10(地下水源限制庆庆庆20, in 庆10(地下水源限制庆庆, in Nitratecase of limited ground water case of limited ground (calculated on nitrogen)source)water source ?20)三庆甲庆 Chloroform /(mg/L)庆0.06庆0.06四庆化碳 Carbon tetrachloride /庆0.002庆0.002(mg/L) 庆酸庆;使用臭庆,氧/(mg/L)庆0.01庆0.01Bromate (For process using ozone) 甲庆;使用臭庆,氧/(mg/L) Formaldehyde (for process using 庆0.9庆0.9 ozone) Fujian Fukang Pharmaceutical Co., Ltd. Page: 17 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 生活庆用水庆生庆准 控制庆目Acceptance criteria of 企 庆 庆 准 Testing itemspotable water in ChinaIn-house criteria GB 5749—2006 庆庆酸庆;使用二化庆消毒庆,氧 Chlorite (for sterilization process 庆0.7庆0.7using chlorine dioxide ) /(mg/L)庆酸庆;使用庆合二化庆消毒氧 庆,Chlorate (for sterilization 庆0.7庆0.7process using chlorine dioxide ) / (mg/L) 3.感官性和一般化指庆 状学Sensory, characters and chemical items 不超庆 15 度不超庆 15 度 色度;庆庆色度庆位,Not more intensely colored Not more intensely Color (Platinum-Cobalt Scale)than degree 15 of reference colored than degree 15 of solutionreference solution 不超庆 1 度 不超庆 1 度;水源庆水技庆件限与条 ;水源庆水技庆件限制庆与条制庆不超庆 3 度, 不超庆 3 度,Not more intensely Not more intensely colored colored than degree 1 of 庆庆度;散色庆庆度庆位,than degree 1 of reference reference solution (not Turbidity degree (color and turbidity solution (not more intensely more intensely colored unit) /NTUcolored than degree 3 of than degree 3 of reference solution, when the reference solution, when water source and purification the water source and technique is limited)purification technique is limited) 臭和味无臭、味异异无臭、味异异 Odor and TasteOdorless and tastelessOdorless and tasteless 肉眼可庆物无无 Visible SubstancesNoneNone pH6.5,8.56.5,8.5 庆 Aluminum/(mg/L)庆0.2庆0.2 庆 Ion/(mg/L)庆0.3庆0.3 庆 Manganese/(mg/L)庆0.1庆0.1 庆 Copper /(mg/L)庆1.0庆1.0 庆 Zinc /(mg/L)庆1.0庆1.0Fujian Fukang Pharmaceutical Co., Ltd. Page: 18 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 庆化物 Chloride /(mg/L)庆250庆250 硫酸庆 Sulphate /(mg/L)庆250庆250 生活庆用水庆生庆准 控制庆目Acceptance criteria of 企 庆 庆 准 Testing itemspotable water in ChinaIn-house criteria GB 5749—2006 溶解性庆固体庆1000庆1000Total soluble solid/(mg/L) 庆硬度;以 CaCO庆,3 Total hardness庆450庆450(Calculated on CaCO)/(mg/L)3 庆3庆3;水源限制～原水耗氧耗量;氧COD Mn 法～以 O;水源限制～原水耗量氧2量>6 mg/L 庆 庆5,庆,COD (COD Mn method, >6 mg/L 庆 庆5,(?5, in case of limited calculated as O)/(mg/L)(?5, in case of limited water 2water source with source with COD>6 mg/L, )COD>6 mg/L, ) 庆庆庆;以庆,酚苯酚 Volatile phenols庆0.002庆0.002(Calculated on phenol)/(mg/L) 庆子合成洗庆庆离庆0.3庆0.3Synthetic Anionic detergent/(mg/L) 4.放射性指庆 Radioactivity items 庆 α 放射性庆0.5庆0.5Total α radioactivity /;Bq/L, 庆 β 放射性庆1庆1Total β radioactivity /;Bq/L, 5.消毒庆指庆 Disinfector itemsFujian Fukang Pharmaceutical Co., Ltd. Page: 19 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 与触水接 30min 后出水厂 中限庆?4mg/L;出水中余厂 量?0.3mg/L;管末梢水中网 余量?0.05mg/L.游余庆离(庆及游庆制庆气离)?4mg/L remaining in outlet Free Chlorine Residue water after contack with 0.05~1.1mg/L(Chlorine and free chlorine water for 30min;preparation)?0.3mg/L remaining in outlet water; ?0.05mg/L remaining in the end of the pipeline. 庆注,企庆庆庆庆告庆只庆臭和味、肉眼可庆物、菌落庆、庆大庆菌群、游余庆;庆及游庆制庆,。体数离气离 其余庆目庆水庆庆庆站庆告。 Note: The testing items conducted in-house are Odor and Taste, Visible Substances, Microbial Count, Total Coliforms and Free Chlorine Residue (Chlorine and free chlorine preparation). The other testing results are shown in the report from local Water Monitoring Institute. 3.工庆及庆庆流程庆 Flowchart of manufacturing process and equipment flowchart 3.1、工庆及庆庆流程庆Flowchart of manufacturing process and equipment flowchart3.1 工庆流程庆 Flowchart of manufacturing process 0036?2C庆斜面;子瓶,36?2C斜面庆子;母瓶,砂土庆子Working slantsMother slantsSand-soil spores9天days10天days 00C37?1C37?1斜面庆子;母,瓶 庆斜面;子,瓶砂土庆子Working slantsMother slantsSand-soil spores9天days10天days 00031~37C31~37C31~37C一庆庆子罐二庆庆子罐三庆庆子罐 1st seed tank2nd seed tank3rd seed tank12~30hr10~26hr28~41hr 000C31~37C31~3731~37C三庆庆子罐一庆庆子罐二庆庆子罐3rd seed tank1st seed tank2nd seed tank28~41hr12~30hr10~26hr 030~37C庆酵罐放罐庆酵液 FermentorHarvest broth85~135hr 030~37C庆酵罐放罐庆酵液 FermentorHarvest broth65~135hr (注,一庆、二庆、三庆庆子庆原材料、庆子或菌庆生庆情况, 罐可以改庆温,庆庆范庆庆22?,37)?Note: The tank temperature during culture is flexible from 22 to 37, dependent on the?? raw materials, culture conditions of spore or mycelium. Fujian Fukang Pharmaceutical Co., Ltd. Page: 20 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 3.2 庆庆流程庆 Equipment flowchart;庆附件 Enclosed overleaf., 3.2 庆庆流程庆 Equipment flowchart;庆附件 See attachment, Fujian Fukang Pharmaceutical Co., Ltd. Page: 21 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4、工庆庆程 Manufacturing process 4.1庆子工庆庆程 Spore manufacturing process4.1.1生庆用庆子斜面制庆 Preparation of working slants4.1.1.1 菌庆系 庆大素生庆菌庆庆庆色小庆庆菌;霉Micromonospora Purpurea,～我公司庆大素生庆霉所用的出庆菌株庆 F54-3～是 1965 年由福建省微生物究研从所西湖庆泥中自然庆化分离所得到的～ #庆庆数次庆代～目前的生庆菌株庆自 1999 年起用的 225 ～其演庆庆程如下所示,The strain of Micromonospora Purpurea is used in gentamicin fermentation. The first generation (69) F54-3 is chosen from the soil in West Lake via natural purification and separation by Fujian Institute of Microbiology. It has been propagated several generations. Finally, Strain (99)-225# has been obtained as producing strain and has been used in the production since 1999. The pedigree of the strain is listed below. ;69,F54-3 #;81,——17 #;82,——1 #;84,——16 #;86,——15 #;88,——24 #;89,——5 #;91,——11 Fujian Fukang Pharmaceutical Co., Ltd. Page: 22 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: #;93,——11-15-23 ###;94,——23-62 ; 95 , —— 23-31 ; 97 , —— 23-18 # ;99,——225 庆庆色小庆庆菌其菌落隆起～有褶庆～菌落干燥或庆～蜡无尖刺～培庆初期菌落呈橙色～然后逐庆庆庆暗橙色～9-10 天庆出褐黑色的庆子庆。庆庆菌庆庆庆～有分很达枝～着生在庆子梗上～庆常分枝成簇。菌庆庆定不易突庆。 Its colony is prominent, folded, dry or ceraceous, and free of thorn. At early stage of culture, the colony is in orange color and gradually become dark orange; brown spore layer is growing up in 9-10 days. Microscopic examination shows that mycelium grows well, including arthrospores and in shape of cluster with branches. It’s genetically stable, and not intent to mutagenesis. 4.1.1.12 培庆基Culture media 序号原材料配比 Serial no.Raw materialsProportion (%) 1可溶性淀粉Soluble starch0.5-1.0 2硝酸庆KNO0.05-0.153 3碳酸庆CaCO0.05-0.153 4庆化庆NaCl0.02-0.1 5硫酸庆MgSO0.02-0.14 6磷酸庆二庆KHPO0.01-0.0524 7天庆冬素L-asparagine0.001-0.005 8庆脂Agar1.0-2.0 9麸皮Bran1.0-2.0 (庆脂,麸皮的配比庆不同庆地和季庆而庆) The proportions of agar and bran vary, depending on the source and season. pH消前庆至7.5 (可用庆庆庆定pH)。 Adjust pH 7.5 prior to addition of calcium carbonate and check with pH paper. 以上培庆基配置配制好后～,每茄个瓶子(容量250ml)分装50 或 65ml～庆庆庆菌湿121?1?C?,30?1分庆～庆菌完庆～冷却至一定度斜放温两瓶待凝固后抽取置37?C?培庆～庆察无菌度。 Fujian Fukang Pharmaceutical Co., Ltd. Page: 23 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: After preparation of culture media, pack 50ml or 65ml of the medium into each 250-ml eggplant-shaped flask. Sterilize at temperature 121?1?C? for 30?1 minutes, allow to cool and incline the flasks to prepare solid slant. Take two flaks and incubate at 37?C? to check microbiological puritymicrobial contamination. 4.1.1.23 庆子接庆Spore inoculation 母制庆,于超庆瓶台工作面上,在火焰保庆下,用无菌接庆棒挑取砂土庆子于茄子斜面培庆基内,先划中庆,后下从两划而上往庆庆匀均庆地庆庆,塞好棉塞。 Preparation of mother slants: At the 100 class operation bench, under protect of flame, use sterile inoculation tool slightly to transfer some sand-soil spore to mother slants, distribute the sand-soil uniformly by drawing lines from left middle to right both sides upwards after stroking a centerline and plug the lid. 子制庆,于超庆瓶台工作面上,在火焰保庆下,用接庆棒庆庆刮下一母斜面庆子～制成瓶 40ml 庆子庆浮液～每新瓶瓶划匀庆茄子斜面加一小勺～由里往外～塞好棉塞。 Preparation of working slants: At the 100 class operation bench, under protect of flame, use sterile inoculation tool slightly to transfer some mother slants spore to prepare 40 ml of spore suspension. Transfer a small quantity of the spore suspension onto each fresh slant in eggplant flasks, distribute the spores uniformly by drawing lines and plug the lid. 4.1.1.34 培庆保存与Incubation and storage 接庆好之斜面扎好后,放 376?12?恒室架温上培庆 (斜面朝下放)～母瓶培庆 10 天～子瓶培庆 9 天。 Mother slants and working slants should be tied and then transfer to the shelves in the thermostated room. Incubate mother slants upside down at 376?12? for 10 days and incubate working slants upside down at 376?12? for 9 days. 接庆好之斜面扎好后,放 37?1?C?恒室架温上培庆 (斜面朝下放) 10 天。 Tie mother slants, then transfer to the shelves in the thermostated room, incubate upside down at 37?1?C? for 10 days. 培庆2,3天后,庆逐庆庆无菌情。瓶况 After incubation for 2,3 days, check microbiological puritymicrobial contamination of every flask. 培庆好的庆子斜面,保存在45?13?C?冰内箱,并庆行庆量庆庆待用。冰两个箱保存期庆定月左右冰个箱保存期庆定不超庆三月。 After maturation, store in a refrigerator at 45?13?C? and check as per the related specification, ready for use. The shelf life of mother slants in refrigerator are below three monthsis about two months. 4.1.1.45 庆量庆庆要求Specification of mother slants生庆用庆子斜面庆保持庆庆庆庆,无庆菌. The mother slants should be of microbiological puritymicrobial contamination, free from Fujian Fukang Pharmaceutical Co., Ltd. Page: 24 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: foreign microbes. 生庆用庆子斜面每批庆抽1,2瓶作生庆能力庆定,母庆庆庆酵效价庆在瓶瓶1400µg /ml以上庆合格, 子庆庆庆酵效价庆在瓶瓶1200µg /ml以上庆合格。 Randomly take 1,2 mother slant from each lot and check their productivity. The fermentation potency of mother slants should exceed 1400µg /ml, while the fermentation potency of working slants should exceed 1200µg /ml. 4.1.2庆生庆瓶能力庆定Test on flask productivity 4.1.2.1培庆基制庆Preparation of media Fujian Fukang Pharmaceutical Co., Ltd. Page: 25 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4.1.2.1.1庆子培庆基Seed culture media 配比 序号Serial no.原材料Raw materialsProportion 1玉米淀粉Corn starch1.0% 2葡萄糖Glucose0.1% 3玉米粉Corn meal1.5% 4硝酸庆KNO0.05%3 5碳酸庆CaCO0.6%3 6庆化庆CoCl1µg /ml2 7蛋白庆Peptone0.2% 8黄豆庆粉Soybean meal1.0% pH自然。 It is not required to adjust pH. 4.1.2.1.2庆酵培庆基Fermentaion culture media 配比序号Serial no.原材料Raw materialsProportion 1玉米淀粉Corn starch5.5% 2黄豆庆粉Soybean meal3.5% 3玉米粉Corn meal1.0% 4碳酸庆CaCO0.65%3 5庆化庆CoCl10µg /ml2 6硫酸庆Ammonium sulfate0.1% 7硝酸庆KNO0.01%3 8蛋白庆Peptone0.4% pH自然。 It is not required to adjust pH. 以上庆两培庆基配置配制好后,每个瓶三角(500ml)分装40ml庆庆庆菌湿121?1?C? 30?1分庆庆用。 After preparation of culture media, pack 40ml of the medium into each 500-ml conical flask. Sterilize at temperature 121?1?C? for 30?1 minutes, allow to cool, ready for use. 4.1.2.2庆瓶培庆(即生庆能力庆定)Flask test 庆子瓶:刮下斜面庆子少量(豆大一小庆)接庆于庆子瓶内培庆基～置庆床上34?2?C?培庆～20,24小庆庆察培庆液外庆和菌庆形庆～如果正常～庆移入庆酵。 Seed flask: Transfer a small piece of mother slant with size as a bean into the seed flask ththcontaining seed media, place on the shaker and incubate at 34?2?C?. At 20,24 hour, check the appearance and mycelia and transfer to fermentation step if it complies. 庆酵,瓶吸取生庆好的庆子液,按15%接庆量接入庆酵培庆基内,置庆床上,34?2?C?培庆4,6天,即瓶可放,庆定生物效价. Fermentation flask: Transfer mature seed culture with 15% inoculum into the fermentation flask containing fermentation media, place on the shaker and incubate at 34?2?C?. At 4thFujian Fukang Pharmaceutical Co., Ltd. Page: 26 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: ,6th day, test the potency. 4.1.3菌庆保存(砂土庆子制庆) Strain storage (preparation of sand-soil spores) 庆了防止生庆菌庆形庆和生庆能力的庆以保异持菌庆的原始形庆和庆定的生庆能力,必庆注意菌庆保 存。目前采用砂土保存法。 Cares should be taken for strain storage in order to maintain the characteristics or productivity of the production strain and prevent from mutation. The sand-soil storage method is adopted. 4.1.3.1砂,取干庆砂～黄来清自水洗、烘干、60目庆庆～用磁庆吸去庆屑即可使用。 Sand: Take some clean sand, clean with portable water, dry, screen and take them passing 60-mesh sieve. Neutralize with sodium hydroxide, clean with water and dry. Remove trace metal with magnet, ready for use. 4.1.3.2土,砂挖田地上腐殖庆少的中性泥土,化于自来水中,取泥水淀、沉研烘干、庆80目 庆庆～可使用即。 Soil: Dig and take some neutral soil with few humus from the field, mix with portable water, precipitate, dry, grind, screen with 80-mesh sieve, ready for use. 取上述砂和土～按2,1体匀装庆混合均～于10×10mm硬庆庆管～每支庆管装1g砂土。配 上大小适中的庆布棉塞～包两扎庆庆布庆～集中包上牛皮庆～庆歇常庆庆菌五次以上～烘干庆用。 Mix pretreated sand and soil (2:1,v, v/v) well, pack 1g in each test tube (10×100nm), plug with cotton plugs and pack with two layers of gauze and kraft paper. Sterilize with moist heat at 0.1Mpa for 30min, intermittently repeat for more than 5 times, then dry and ready for use. 4.1.3.3砂土庆子制庆Preparation of sand-soil spores 于超庆台工作面上,挑取菌落表面上的庆子,放入庆有玻璃珠的无菌水里,打散,制成庆子庆浮 液。打庆砂土管上庆布及棉塞～用1ml吸管吸取0.1ml庆子庆浮液放入砂土管。内塞庆砂土管 内罩两扎内真棉塞～上庆庆布～用棉庆在庆庆庆。放庆干燥器～用空庆抽干;4-6小庆,～干燥 后之砂土庆子,庆上菌庆名称,代及制庆日期号,保存在5?33-5?C?冰箱中,保存期一年至三 年。使用前庆庆定生庆能力和无菌庆庆,合格者用于生庆。 At the operation bench under the laminar flow, transfer spores from slants in sterile water containing several beadings, shake violently to obtain spore suspending liquid. Transfer 0.1ml of the spore suspending liquid with 1ml pipet into each sterile sand-soil tube. Plug with cotton plugs and pack with two layers of gauze and tie with cotton strands on the tube neck. Place in a desiccator and dry under vacuum for 4-6 hours. After drying, label with strain name, code number and preparation date, store in a refrigerator at 5?33-5?C? and use within 1 to 3 years. Prior to use, check the productivity and microbiological puritymicrobial contamination, and only those pass the tests are put into production. Fujian Fukang Pharmaceutical Co., Ltd. Page: 27 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4.2庆酵工庆庆程 Fermentation manufacturing process 4.2.1工庆件 条Process Conditions Fujian Fukang Pharmaceutical Co., Ltd. Page: 28 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4.2.1.1培庆基配比 Proportion of media 配比% Proportion中庆庆料一庆庆子罐二庆庆子罐三庆庆子罐庆 酵 罐Additional stndrd1 seed tank2 seed tank3 seed tankFermentormedia名称 Raw material 葡萄糖0.05-0.150.2-0.4///Glucose 玉米淀粉0.5-1.51.0-2.54.0-7.04.0-7.04.0-7.0Corn starch 玉米粉1.0-2.01.0-2.50.5-2.50.5-2.50.5-2.5Corn meal 蛋白庆0.1-0.30.1-0.30.3-0.70.3-0.70.3-0.7Peptone 黄豆庆粉0.5-1.51.0-3.02.0-4.02.0-4.02.0-4.0Soybean meanl 硝酸庆0.04-0.1/0.01-0.020.01-0.020.01-0.02Potassium nitrate 硫酸庆//0.05-0.150.05-0.150.05-0.15Ammonium sulfate 碳酸庆0.5-0.70.3-0.60.5-1.00.5-1.00.5-1.0Calcium carbonate 泡庆//13-3 9 L124-15 L3-9 L1-3LDefoamer 淀粉庆(w/w)//0.005-0.0150.005-0.0150.005-0.015Amylase 庆化庆1-3ug/ml5-10ug/ml6-15 ug/ml6-15 ug/ml6-15 ug/mlCobalt chloride 庆料庆体01.68-248-1645-248-33.59-124m33333333Volume transferred20.7m1m 10m30m 20m60m 10m30m 1.8-3333消后庆体9-12m 3.5-24-30m 8-45-60m 16-24-30m 8-32.1m 0.6-0.7 3333Volume received4m10m20m10m3m 注1,根据原材料庆量和源可庆来整配比(庆培庆基配比表)。 Note1: Adjust proportion as per quality and source of raw materials, see table above. 注 2,淀粉庆用量=;玉米淀粉用量+玉米粉用量,×配比% 4.2.1.2.培庆基消毒要求培庆基庆菌要求 Sterilization requirement of culture media 4.2.1.2.11 庆子罐培庆基消毒庆菌温度121?C???1?C～罐庆 0.1MPa??保温30?1分庆,庆酵罐及全料消毒度温庆酵罐及庆料庆菌度温 121???1?～罐庆 0.1MPa 保温15?1分庆庆底庆菌。 Seed media: sterilize at 121?C???1?C～0.1MPa? for 30?1min; Fermentation media and additional media: sterilize at 121?C???1?C～0.1MPa? for 15?1min. Fujian Fukang Pharmaceutical Co., Ltd. Page: 29 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4.2.1.2.2二、三庆庆子罐,庆酵罐培庆基消毒后庆酵罐培庆基庆菌后,需用液庆庆碱pH至7.0,7.5～庆庆pH庆培庆基度庆在温45?C??以下,方可加。碱 After sterilization of 2nd seed, 3rd seed and fermentation media, allow to cool to below 45?C??, adjust pH 7.0,7.5 with alkali. 4.2.1.3 庆庆及庆量Seed age and inoculum percentage4.2.1.3.1庆子移出庆准Specification for seed culture 罐庆一庆庆子罐二庆庆子罐三庆庆子罐stndrdTank1 seed tank2 seed tank3 seed tank 庆庆28,40hr12,30hr10,26hrSeed age 菌庆形庆呈中庆～状染色深～ 有少量粉段枝呈中庆状 菌庆,染色深,有少量粉呈网状,菌庆量多,芽枝呈密网状,菌庆量多,芽段枝形庆多枝多Mycelium morphology is Microscopic Large quantity of net-Large quantity of net-middle lumpish, in deep characteristics shaped mycelia, with shaped mycelia, with color, with short pieces of sprout branches.sprout branches.hyphaCulster-formed mycelia, with deeply dyed color and some short branches. 浅黄灰色,庆子液粘稠,庆浅黄灰色,庆子液庆庆能庆能着壁着壁外庆微灰色黄淡色黄Yellowish-grey color, Yellowish-grey color, AppearanceYellowish-grey colorviscid, seed culture seed culture adhesive adhesive to the wall to the wall once stirredonce stirredFujian Fukang Pharmaceutical Co., Ltd. Page: 30 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 4.2.1.3.2接庆量 Inoculum percentage 罐庆一庆庆子罐二庆庆子罐三庆庆子罐庆酵罐stndrdTank1 seed tank2 seed tank3 seed tankFermentor 接庆量1030 瓶/罐 Inoculum 10 30 working 13,17%29,37%38,48% percentageslants / tank 4.2.1.4培庆件条Culture conditions 4.2.1.4.1罐温Tank temperature 一、二、三庆庆子罐均31,37?C??培庆。 1st, 2nd, 3rd tank: incubate at 31,37?C?. 注:可根据生庆情况当温适升降,一、二、三庆庆子罐罐温最高不能超庆37?C??,最低不能低于22?C??。 Note: The temperature is adjusted as per the culture growth conditions, with the highest limit at 37?C? and lowest limit at 22?C??. 庆酵罐:30,37??培庆。 Fermentor: incubate at 30,37?C??. 4.2.1.4.2罐庆Tank pressure 一庆庆子罐1st seed tank: 0.03,0.05Mpa 二庆庆子罐2nd seed tank: 0.02,0.04MPa三庆庆子罐3rd seed tank: 0.01,0.04MPa 庆酵罐Fermentor: 0.01,0.04MPa4.2.1.4.3空气流量Aeration 一庆庆子罐1st seed tank: 52%,68%0.9,1.2m3/min (1?1.3-1.7 v/v)二庆庆子罐2nd seed tank: 6578%,85100% (1?1.3-1.7 v/v) 三庆庆子罐3rd seed tank: 6665%-10098% (1?1.0-1.5 v/v) 庆酵罐Fermentor: 2060%-40100% (50m3 罐 tank)、35%-75%;60m3 罐 tank,(1?1.0-1.5 v/v) 4.2.1.4.4 pH庆 一庆庆子罐1st seed tank: 6.5-7.5 二、三庆庆子罐2nd and 3rd seed tank,7.0-7.5 庆酵罐Fermentor: 6.5-7.5 4.2.2庆酵中庆庆料In-process media addition4.2.2.1庆始庆料庆庆Starting point of mida media addition 庆酵液泡沫下降后2,3小庆,菌庆生庆良好,庆酵液化呈色并浅黄,此庆可以庆料。2,3 hours after fermentation broth foams decline, mycelia grow well and fermentation broth appears liquified and yellowish, start to add media . 4.2.2.2庆料庆庆和次数Addition point and frequency庆按糖、基代庆庆庆情庆行控制庆料～在一般情下氨氮况况,可按下列庆法, 33庆酵8,20小庆庆全料824,10m30m ～庆酵20小庆后庆代庆情况,、液面高低可庆2-5次水～ 3每次 1.5~10 m ～遇代庆异号体常或不正常批可按具工庆要求庆行庆料。 Fujian Fukang Pharmaceutical Co., Ltd. Page: 31 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: Add media according to metabolism of sugar and ammonium nitrogen. Under normal circumstances add media as follow: 3At 8th ,20th hour of fermentation, add 824,130m of media. After 20 hours of fermentation, according to the metabolism and volume of broth, add water 2-5 times, each 3time 1.5-10m . In case of abnormal metabolism and batches, add media or water as required.4.2.3空气的供庆Air supply 4.2.3.1 整个气庆子生庆和庆酵生庆庆程中要保庆通入一定量的无菌空。 A suitable volume of sterile air is supplied in the whole process of seed growth and production fermentation. 4.2.3.2 空气未入庆庆前,空气温度庆在 30?以下,并庆加庆至4035,45?C??,降低空气湿的 度,防止介庆潮。湿 Before tThe air supply arrives the workshop system, its temperature should be controlled below 30?. Then the air is heated to 4035,45?C?? to reduce its humidity and prevent cartridge from moist. 4.2.3.3 空气玻粗庆庆器每半年更庆一次庆庆介庆;璃棉～棉花,。 Pre-filter for air: change cartridge (glass cotton and cotton) every half a year.4.2.3.34 空气庆庆庆器庆膜庆庆器,每三月个更庆一次介庆 。 First filter for air: change membrane cartridge every three months.4.2.3.45 空精气庆庆器庆膜庆庆器,每两年更庆一次介庆,每三月消毒一个次。 Second filter for air: change membrane cartridge every two years and sterilize every three months. 4.2.3.56 蒸汽庆庆器介庆每两年更庆一次。 Steam filter: change cartridge once two years. 4.2.4通 氨Addition of ammonium hydroxide 4.2.4.1庆用18,20%以上氨水,氨内静水在庆罐必庆置 7 天后才能使用。 Preparation of of 18,20% ammonium hydroxide whichwith concentration of more than 18%: Allow to stand in the holding tank for 7 days prior to use. 4.2.4.2通庆庆氨:庆酵罐培庆至24小庆以后(庆酵液已庆色)氨氮基降至40mg40mg/100ml以下 可以庆代庆情庆行通况氨,每4小庆庆定基定通量氨氮决氨,最多一次不能超庆15L40L。 Addition frequency: After 24th hour of fermentation, the fermentation broth changes color and ammonia nitrogen decreases to below 40mg40mg/100ml, start to add ammonium hydroxide according to the metabolismappropriately. Test ammonia nitrogen every 4 hours and decide the addition volume with the upper limit of 15L40L. 4.2.4.3通由菌氨霉当室班人庆庆出指令庆班庆庆行但必庆二人操作。 The person from the in-process group gives instructions of adding ammonium hydroxide and two workers from the duty group add ammonium hydroxide. 4.2.5庆酵中庆庆定体In-process test of fermentation 4.2.5.1庆子罐,消后、移出庆糖、基、氨氮pH、中庆每隔 12 小庆庆一次 pH、基氨氮,每4,6小庆 Fujian Fukang Pharmaceutical Co., Ltd. Page: 32 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 取庆度庆庆庆品无庆,并涂况片庆庆生庆情。 Seed tank: sugar, ammonia nitrogen and pH are is tested after sterilization and when transferring to next step; ammonia nitrogen and pH are tested every 12 hours during incubation, microbiological puritymicrobial contamination test and microscopic test of smear are performed every 4,6 hour. 4.2.5.2庆酵罐,接后从到放罐每12小庆庆一次庆糖、基、氨氮pH、生物效价;36小庆庆始庆 定,,40 小庆前每 6 小庆取无庆,40 小庆后每12小庆取庆度庆庆庆品无庆直至放罐前一天,～50小庆 前每12小庆涂片庆庆。 Fermentor: total sugar, ammonia nitrogen and pH are tested after seeding and every 12 hours during fermentation, potency is tested every 12 hours during fermentation (starting from 36th hour), microbiological puritymicrobial contamination is tested every 6 hours at the beginning 40 hours and every 12 hours until one day before harvest, microscopic test of smear is performed every 12 hours at the beginning 50 hours.4.2.5.3庆度庆庆无庆庆品庆庆三庆品庆庆菌个,庆涂即片形庆一致可庆出染菌MATCH_ word word文档格式规范word作业纸小票打印word模板word简历模板免费word简历 _1714206510590_0庆。 If foreign microbes are found on three consecutive samples in microbiological puritymicrobial contamination test and it is confirm that the microscopic descriptions are identical, the notification of microbiological contamination is issued and sent out. 4.2.6 庆酵庆点的判断,庆酵周期 80~135 小庆～放罐效价?700ug/ml～庆糖 0.5~1.5g/100ml～庆度符合庆定～完全符合以上庆准可放罐。即 The fermentation will be stopped between 80-135 hours when the fermentation broth is in compliance with following requirements: potency?700µg/ml, total sugar falling within 0.5-1.5g/100ml, free from microbial contamination. 5、中庆控制庆品的庆量庆准和庆庆方法 Specification and analytical methods of in-process materials5.1中庆控制庆品的庆量庆准Specification of in-process materials 庆 庆 Contents 庆 目庆量庆准Acceptance criteria Items 庆酵效价?700ug/ml;放罐庆at harvest,Fermentation potency 无菌度庆度 Microbiolocial 符合庆定Must comply puritycontamination pH6.5,7.5 th?2.5g/100ml;40小庆前before 40 hour,～庆糖th0.5~3.0 g/100ml;40 小庆后 after 40 hour ,Total sugar?0.5~1.50.5g/100ml;放罐庆at harvest, 氨氮基th20-50mg/100ml;24小庆后after 24 hour,Amonia nitrogen Fujian Fukang Pharmaceutical Co., Ltd. Page: 33 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 5.2中庆庆品的庆庆方法中庆控制的庆庆方法 Analytical methods of in-process materials5.2.1庆大庆酵液pH的庆定pH test of gentamicin fermentation broth将匀待庆庆品庆拌均,依照pH庆使用庆准操作庆程庆程;FASOP-QC-067,庆行庆定。 Stir the sample to be determined and mix well. The pH is determined according to the SOP for Use of pH meter. ;FASOP-QC-067,. 5.2.2庆大庆酵液罐上涂与片庆庆Smear and microscopic test of fermentation broth滴滴庆酵液几玻到片(庆75×25mm)上,庆酵液太庆庆涂片要用蒸庆水稀庆,不宜涂得太厚,,80- 100?干燥固定,待片冷却后用0.1%美庆液染色30-60秒,用自来冲水洗后在 80-100?干 燥,注意自来玻水流速要庆而庆慢。在片上滴一滴香柏油, 采用10倍目庆和100倍物庆;油 庆,庆微庆庆庆。 Smear the fermentation broth on a slide (about 75×25mm), dilute with purified water if the fermentation broth is stiff. The smear should be appropriately thin. Dry and fix at 80-100?, allow to cool, stain with 0.1% methylene blue solution for 30-60 seconds, wash with potable water and dry at 80-100?. During washing, the potable water flow is controlled to be small and slow. Then add one drop of cedar oil, place the slide under the microscope and exam with 10-time eye lens and 100-time objective lens.5.2.3糖的庆定Sugar test content 5.2.3.1 糖庆准曲庆的制作 Standard curve of sugar, 5.2.3.1.1 称取无水葡萄糖;AR 庆庆庆～庆先庆 105?C 干燥 2 小庆,5.0 克～精密定～加庆化称 水溶解后庆移至 100ml 容量中～加水瓶匀确稀庆至刻度～庆。分庆准吸取庆溶液 0.1ml、0.2ml、0.3ml、0.4ml、0.5ml、0.6ml、0.7ml～于 150ml 三角瓶中～加水 5ml～各准确 加入 20ml 混合庆庆液～置庆上加庆至炉并沸庆保持 3 分庆～取出～冷却～加入 2mol/L 硫酸 溶液 15ml～立即以 0.1mol/L 硫代硫酸庆滴定液滴定至溶液呈淡色～加黄 1%淀粉指示 液 1ml～庆庆滴定至庆色消退～庆庆点～庆取消耗硫代硫酸庆滴定液的即数并毫升～庆庆。;每 一庆度做平双份行庆庆～取平均庆, Place about 5.0 g of Glucose anhydrous (Grade RA, before use dry it at 105?C for 2 hours) accurately weighed. Dissolve it in some purified water before transferring to 100 ml of volumetric flask, dilute to volume with water and mix well. Respectively pipet accurate 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.5 ml, 0.6 ml and 0.7 ml of the solution to seven 150 ml of conical flasks, separately add 5 ml of water and 20 ml of mixed copper TS. Heat the flasks on electric cooker, boiling for three minutes. After cooling, to the flask add 15 ml of Sulfuric Acid Solution (2 mol/L), immediately titrate it with 0.1 mol/L sodium thiosulfate VS (Na2S2O3) till pale yellow color appears, add 1 ml of 1% starch indicator, continue titrate till blue color fades. Record the volume of consumed thiosulfate VS. (Perform double parallel tests on each concentration, average the results) 5.2.3.1.2 空白溶液的庆定,另取庆化水 5ml 代替庆品～同法庆庆～双份平行庆定～取平均庆作 Fujian Fukang Pharmaceutical Co., Ltd. Page: 34 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 庆空白庆定庆。 Determination of blank solution: Replace the sample solution by 5 ml purified water. Perform the same double parallel tests. Average the results as the blank test result. 5.2.3.1.3 以空白消耗硫代硫酸庆滴定液庆庆体减去庆品所消耗的 0.1mol/L 硫代硫酸庆滴定液毫升数的差庆庆庆坐庆;ml,～以相庆之糖含量庆横坐庆(g)～制作出糖庆准曲庆的回庆方程～相庆系数 R2?0.9900。y=bx+a Calculate the difference of 0.1 mol/L sodium thiosulfate VS consumed by blank solution and by the sample solution titration. With the difference as horizontal ordinate and the corresponding sugar as vertical ordinate, draw the standard curve and work out the regression equation: y=bx+a, with the correlation coefficient R2?0.9900.5.2.3.2 庆庆操作 Testing procedure, 5.2.3.2.1 庆糖庆定 Total sugar determination, 将庆酵液用庆庆庆庆于干燥的庆管中～吸取庆液 1ml 于 150ml 三角瓶并中～加入 3mol/L 庆酸溶液 10ml～置庆上加庆至炉并沸庆保持 3 分庆～取下冷却后加入庆指示液酚 3 滴～以 3mol/L 庆氧确化庆溶液中和至淡庆色～再准加入混合庆庆液 20ml～置庆上加庆至炉并沸庆保持 3 分庆～取出～冷却～加入 2mol/L 硫酸溶液 15ml～立即以 0.1mol/L 硫代硫酸庆滴定液滴定至溶液呈淡色～加黄 1%淀粉指示液 1ml～庆庆滴定至庆色消退～庆庆点～庆取消耗硫代硫酸庆即 滴定液的毫升数并～庆庆。 Filtrate the fermentation broth to a dry tube. To 150 ml of conical flask, add 1 ml of filtrate and 10ml of 3 mol/L hydrochloric acid; after heating to boil and keeping for 3 minutes, cool. Add 3 drops of phenothalin indicator and neutralize to pale red with 3 mol/L Sodium hydroxide solution, then accurately add 20ml of mixed cupper TS and heat to boil on an electric furnace and keep for 3 minutes, cool. Add 15ml of 2 mol/L sulfuric acid and immediately titrate with 0.1 mol/L sodium thiosulfate VS (Na2S2O3) till pale yellow color appears, add 1 ml of 1% starch indicator, continue titrate till blue color fades. Record the volume of consumed thiosulfate VS.5.2.3.2.2 空白溶液庆定同 5.2.3.1.2。 Determination of blank solution is the same to 5.2.3.1.2.5.2.3.3 庆算 Calculation, 空白消耗硫代硫酸庆滴定液毫升去数减数将庆品消耗硫代硫酸庆滴定液毫升～差庆代入糖庆准曲庆的回庆方程～庆算出糖含量。 Calculate the difference of 0.1 mol/L sodium thiosulfate VS consumed by blank solution and by the sample solution titration. Put the difference into the regression equation to obtain the sugar content. aY-1××100庆糖含量 Total sugar content;g/100,=bV 将庆酵液庆庆,吸取庆液 1ml,并加入 3mol/L 庆酸溶液 10ml,置庆上加庆至炉并沸庆保持 3 分庆,取Fujian Fukang Pharmaceutical Co., Ltd. Page: 35 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 下冷却后加入庆指示液酚 3 滴,以 3mol/L 庆化庆溶液中和至淡庆色氧,再准加入混合庆庆液确 20ml,置庆上加庆至炉并沸庆保持 3 分庆,取出,冷却,加入 2mol/L 硫酸溶液 15ml,立即以 0.1mol/L 硫代硫酸庆滴定液滴定至溶液呈淡色黄,加 1%淀粉指示液 1ml,庆庆滴定至庆色消 退,即庆庆点,庆取消耗硫代硫酸庆滴定液的毫升数,并庆庆。同法庆定空白～用空白消耗硫代硫 酸庆滴定液毫升去数减数庆品消耗硫代硫酸庆滴定液毫升～庆算出糖含量。 To 1 ml of filtrate of fermentation broth, add 10ml of 3 mol/L hydrochloric acid; after heating to boil and keeping for 3 minutes, cool. Add 3 drops of phenothalin indicator and neutralize to pale red with 3 mol/L Sodium hydroxide solution, then accurately add 20ml of mixed cupper TS and heat to boil on an electric furnace and keep for 3 minutes, cool. Add 15ml of 2 mol/L sulfuric acid and immediately titrate with 0.1 mol/L sodium thiosulfate VS (Na2S2O3) till pale yellow color appears, add 1 ml of 1% starch indicator, continue titrate till blue color fades. Perform blank titration using water for correction.Total sugar is calculated using the difference between the volume (ml) of sodium thiosulfate VS consumed in blank titration and that consumed in sample titration.5.2.4氨氮基的庆定Ammonia nitrogen test 庆酵液庆庆～吸取庆液5ml～加庆化水50ml,加0.1%甲基庆指示液2-3滴,用0.1mol/L硫酸溶 液滴定至庆色不再消失,然后用0.1mol/L庆化庆滴定液滴定至庆色庆氧退,加入18%的中性甲 庆溶液5ml,庆匀,加入庆指示液酚3-4滴,用0.1mol/L NaOH滴定液滴至溶液庆庆色。1毫升的 0.1mol/L庆化庆滴定液氧当相于14 mg氨氮氨氮基～庆酵液中基以mg/100 ml庆。 To 5 ml of filtrate of fermentation broth, add 50 ml of purified water and 2-3 drops of 0.1% methyl red indicator, titrate with 0.1 mol/L sulfuric acid until red color is permanently produced, then titrate with the 0.1 mol/L Sodium hydroxide VS till red color just disappears, add 5 ml of 18% neutral formaldehyde solution and 3~4 drops of phenothalin indicator, titrate with the 0.1 mol/L Sodium hydroxide VS until the red color just reappear. Per ml of 0.1of 0.1 mol/L Sodium hydroxide VS is equivalent to 14 mg of nitrogen and ammonia nitrogen in fermentation broth is calculated as mg/100 ml.5.2.5庆大素中庆生物庆定法霉体Potency test of gentamicin fermented broth 5.2.5.1 培庆基 Media 5.2.5.1.1 庆庆庆脂培庆基Nutrient agar medium (pH7.2-7.4): 采用干粉培庆基或按以下配方制庆。 Use dry powder media and prepare as per the following proportion. 庆Peptone 10g 庆化庆Sodium Chloride 5g 庆 脂Agar 15-20g *肉浸液Beef extract solution 1000ml *可以用3g牛肉浸出粉加水至1000ml配制。 Preparation alternatively: Dissolve 3 g of beef extract in water and complete to Fujian Fukang Pharmaceutical Co., Ltd. Page: 36 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 1000 ml with water. 5.2.5.1.2培庆基Medium I (PH7.8-8.0), 采用干粉培庆基或按以下配方制庆。 Use dry powder media and prepare as per the following proportion. 庆Peptone 5g 牛肉浸出粉Beef extract 3g 酸庆二庆磷Dipotassium hydrogen phosphate 3g 庆脂Agar 15-20g 水Water 1000ml 5.2.5.2 庆菌庆液冲Sterile buffer solution 磷冲酸庆庆液(PH7.8): 取酸庆二庆磷5.59g与磷酸二庆庆0.41g,加水使成1000ml,庆庆,在 115??C 庆菌30分庆。 Phosphate buffer (pH 7.8): Dissolve 5.59 g of dipotassium hydrogen phosphate and 0.41 g of potassium dihydrogen phosphate in water and complete to 1000 ml with water, filter, sterilize at 115?C? for 30 minutes. 5.2.5.3 菌庆液制庆Preparation of test microorganism suspension 取短小芽庆杆菌[CMCC(B)63202]庆庆庆脂斜面培庆物, 接庆于盛有庆庆庆脂培庆基的茄瓶斜面上, 在36?1?C?培庆七日,用庆菌水将芽庆洗下, 65?C?加庆30分庆,菌庆液2-8?C?可存用1 个径月。菌庆液加量以庆得大小合适的抑菌圈庆准。;高庆度所致的抑菌圈直庆庆18-22mm, Inoculate Bacillus Pumilus [CMCC (B) 63202] on nutrient agar medium; incubate at 36?1?C?C for 7 days. Then wash the spores with sterilized water, and heat at 65?C for 30 minutes. The suspension could be stored at 2~8?C?C for up to one month. The augment of bacterial suspension should be suitable so that satisfactory demarcation of the inhibition zone is acquired. (The inhibition zone induced by the high dosage should be 18-22mm in diameter.) 5.2.5.4双碟制庆Preparation of Petri dishes 将培庆基I水浴庆融,用大口吸管向置于无菌水平台板上的注入双碟内培庆基20ml,使之在 碟匀底均庆布,待凝固后;庆30分庆,,另取部分庆60?C?的培庆基加入菌庆液适量,庆匀,分庆 向每碟注入含菌培庆基5ml,迅速旋庆使之在碟匀底均庆布庆菌庆,置水平台上凝固。 Melt medium I in hot water bath, transfer 20 ml of the medium into each Petri dish on the sterile operation bench using pipette, shake to distribute the medium evenly at the bottom of the dish, allow to solidify (for about 30 minutes). Into the medium at about 60?C, add a suitable amount of bacterial suspension and shake well. Separately inject 5 ml of the medium containing bacteria to each Petri dish, and shake well while warm. Quickly place them on a flat level surface to obtain a layer of evenly distributed medium containing bacteria. 5.2.5.5溶液的制庆Preparation of solutions Fujian Fukang Pharmaceutical Co., Ltd. Page: 37 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 5.2.5.5.1庆准品溶液:精密取庆大素庆准品称霉适量,按庆示效价用水溶解稀庆成1000µg/ml 溶液,此液在2-8?C?中可存用一周,庆用前再用酸庆庆液;磷冲pH7.8,其将稀庆成2.0- 12.0µg/ml范庆的内两个当适庆度。 Preparation of Gentamicin sulfate Standard solution: accurately weigh a proper amount of Gentamicin sulfate Standard, dissolve and dilute to 1000 μg/ml with water according to the labeled potency(as is), the stock solution can be stored at 2-8?C? for up to 7 days. Prior to use, dilute to the two appropriate concentrations within 2.0~12.0 μg/ml with phosphate buffer (pH 7.8). 5.2.5.5.2庆品溶液:将霉所送庆的庆大素庆酵、提庆中庆庆品用庆硫酸(化庆或分学析庆)酸化至 pH2.0左右,按罐庆序号号排列庆,放置15-20分庆后,再庆庆,留庆密封庆存2-8?C?。庆用庆依庆庆庆估 效价,用酸庆庆液磷冲确与两个精稀庆至庆准品溶液相庆的庆度。 Preparation of sample solution: Acidify fermented broth or purification in-process product to pH 2.0 with sulfuric acid (C.P. or A.R.), number according to fermentor no. Stand for 15-20 minutes, filter, seal the remained sample and store at 2~8?C. Prior to use, accurately dilute to the two concentrations corresponding to the concentrations of the standard solution with phosphate buffer according to assumed potency of the test sample. 5.2.5.6溶液点庆Sample application 向制好的培庆皿中按正四庆形放置4只小庆管,并作好庆庆。向庆角的二只小庆管滴加高、低庆量 庆准品溶液;向另二只小庆管滴加高、低庆量庆品溶液。 Place four steel tubes (Oxford cylinder cups) into a prepared plate and arrange as the four vertexes of quadrate and labeled. Apply the standard solution of high and low dosage into the two steel tubes in diagonal position and apply the sample solution of high and low dosage into another two steel tubes. 5.2.5.7双碟培庆Petri dishes incubation 将滴好的培庆皿加陶盖小心移入36?1?C?培庆14-16小庆,得出大小适合庆庆的清晰抑菌圈 后取出庆量其直径份数或面庆;每庆庆培庆皿目不少于4个,。 After applying the sample in Petri dishes, carefully transfer the covered Petri dishes into the incubator and incubate at 36?1?C?C for 14-16 hours. Measure the diameter or area of bacterial inhibition zone when proper-size zones with sharp borders are obtained (Not less than 4 dishes are used in each test). 5.2.5.8庆算和庆告Calculation and report 5.2.5.8.1庆算公式Calculation formula :,U+U?S?S?1HLHL,,P=log×I×100% P= A×Ptt,,U+S?U?S:HHLL: P----相庆效价Relative potency;%, I----抗生素高低庆度比庆的庆数Logarithm of ratio of high dosage to low dosage S----庆准品高庆度液所致的抑菌圈直之径和 Sum of diameters of the bacterial H Fujian Fukang Pharmaceutical Co., Ltd. Page: 38 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: inhibition zone resulted from high dosage of standard solution;mm,～ S----庆准品低庆度液所致的抑菌圈直之径和Sum of diameters of the bacterial L inhibition zone resulted from low dosage of standard solution;mm,～ U----庆品高庆度所致的抑菌圈直之径和Sum of diameters of the bacterial inhibition H zone resulted from high dosage of sample solution;mm,～ U----庆品低庆度所致的抑菌圈直之径和Sum of diameters of the bacterial inhibition L zone resulted from low dosage of sample solution;mm,～ P----庆品庆庆效价Actual potency;庆g/mg,t A----庆品庆效价估Estimated potency;庆g/mg,t 5.2.5.8.2庆庆要求Acceptance criteria of statistics每份数庆庆庆据～其回庆庆庆非常庆著;P,0.01,,偏平离行庆不庆著;P,0.05,,平均可信限率庆不大于10%。 For each portion of experiment data, regression should be very remarkable (P<0.01), and deviates from parallel should not be remarkable (P>0.05). The average rate of confidence limit should be not more than 10%.6、三庆庆理Waste treatment 庆液庆往庆水庆理站庆理。 Waste liquid is sent to Waste water treatment workshop for disposal.Fujian Fukang Pharmaceutical Co., Ltd. Page: 39 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 7、主要庆庆一庆表Equipment list 2101701 庆庆 Workshop No. 2101701 序号庆庆位号庆庆名称容 量数量材 庆No.ID ?EquipmentCapacityQtyMaterial #31 5m1配料罐1S.S.#32 Proportioning tank10 m 1 一庆庆子罐332201~208511-514 5 m 84S.S.S.S.20 mst1 Seed tank 一庆庆子罐 二庆庆子罐333501-508611-61435 m 20 m 84S.S.S.S.nd 2 Seed tank 二庆庆子罐 三庆庆子罐334701-710711-71580 m 60 m 105S.SA3.rd3 Seed tank 三庆庆子罐3150 m 150 庆酵罐5801-810813-818106S.S.S.S.3Fermentor 庆酵罐m 3313~316庆水罐 Addition tank 庆水罐7m 46S.S.S.S.33601~604615-618Addition tank35 m 10 m 44 Fujian Fukang Pharmaceutical Co., Ltd. Page: 40 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 701 庆庆 Workshop No. 701 序号庆庆位号庆庆名称容 量数量材 庆No.ID ?EquipmentCapacityQtyMaterial #31 5m1配料罐1S.S.#32 Proportioning tank10 m 1 一庆庆子罐3321511-514201~208 20 m 48S.S.5 mst1 Seed tank 二庆庆子罐332611501-6145082035 m 48S.S.nd 2 Seed tank 三庆庆子罐34371101-7150 510S.SA3.6080 mrd3 Seed tank 庆酵罐35481301-8180150 m 610S.S.Fermentor 3615313~316-618庆水罐 FermentorAddition 107 m 465S.S.3601~604tank35 m 4 序号庆庆位号庆庆名称容 量数量材 庆No.ID ?EquipmentCapacityQtyMaterial #31配料罐4.5m11AR3#32Proportioning tank10 m1 601-604,一庆庆子罐322.5 m6S.S.st606, 6081 Seed tank 3二庆庆子罐10 m6 3701-708S.S.nd 32Seed tank15 m2 3三庆庆子罐20 m3 4901,904-906S.S.rd33 Seed tank30 m1 801-804,庆酵罐3550 m10AR3807-812Fermentor 庆酵罐36805-80660 m2AR3Fermentor 101 庆庆 Workshop No. 101 序号庆庆位号庆庆名称容 量数量材 庆No.ID ?EquipmentCapacityQtyMaterial #1配料罐314.5m2S.S.#2Proportioning tank 32201-203,205一庆庆子罐5 m4S.S.Fujian Fukang Pharmaceutical Co., Ltd. Page: 41 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: st1 Seed tank 二庆庆子罐33206-2094S.S.10 mnd 2Seed tank 三庆庆子罐34503-5064S.S.30 mrd3 Seed tank 庆酵罐35301,302,307,30860 m4AR3Fermentor 庆酵罐36303-30660 m4S.S. Fermentor Fujian Fukang Pharmaceutical Co., Ltd. Page: 42 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: Fujian Fukang Pharmaceutical Co., Ltd. Page: 43 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: Fujian Fukang Pharmaceutical Co., Ltd. Page: 44 硫酸庆大素庆酵工庆庆程 霉 文件号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 8、庆算公式Calculation formula 8.1、平均庆酵庆位Mean Potency (µg /ml) 庆酵液庆庆Fermentation broth activity (µg) = 庆酵液庆庆体Fermentation broth volume(ml) 38.2、平均放罐庆体Mean harvest volume (m) 3庆酵庆庆体Total fermentation volume (m) = 放罐庆批数Total batches 8.3、平均庆酵周期Mean fermentation cycle (hr) 庆罐周期之和Sum of fermentationo cycle = 放罐庆批数Sum of batches 8.4、大罐庆酵染菌率Microbiological contamination percentage of fermentation (%) 庆酵(罐)染菌批数Batches of microbiological contamination = ×100% 庆菌批次Batches of sterilization 38.5、庆酵指数Fermentation index (庆酵液庆庆Fermentation broth activity /小庆hr•m) 平均庆酵庆位Mean Potency×平均放罐庆体Mean harvest volume = 平均庆酵周期Mean fermentation cycle×庆酵罐容庆Fermentation capacityFujian Fukang Pharmaceutical Co., Ltd. Page: 45 硫酸庆大素庆酵工庆庆程 霉 文件 号:: FATS-PP-F(J-J701)-GMC-1-1 Fermentation Process Procedure of Gentamicin Sulfate Document Code: 9、附庆 Attachments Fujian Fukang Pharmaceutical Co., Ltd. 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